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论文题目: O-GlcNAcylation of fumarase maintains tumour growth under glucose deficiency
英文论文题目: O-GlcNAcylation of fumarase maintains tumour growth under glucose deficiency
第一作者: Wang, T; Yu, QJ; Li, JJ; Hu, B; Zhao, Q; Ma, CM; Huang, WH; Zhuo, LG; Fang, HQ; Liao, LJ; Chin, YE; Jiang, YH
英文第一作者: Wang, T; Yu, QJ; Li, JJ; Hu, B; Zhao, Q; Ma, CM; Huang, WH; Zhuo, LG; Fang, HQ; Liao, LJ; Chin, YE; Jiang, YH
联系作者: Wang, T; Jiang, YH (reprint author), Shanghai Jiao Tong Univ, Inst Cell Metab, Shanghai Gen Hosp, Shanghai Key Lab Pancreat Dis,Sch Med, Shanghai 200080, Peoples R China.
英文联系作者: Wang, T; Jiang, YH (reprint author), Shanghai Jiao Tong Univ, Inst Cell Metab, Shanghai Gen Hosp, Shanghai Key Lab Pancreat Dis,Sch Med, Shanghai 200080, Peoples R China.
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发表年度: 2017
卷: 19
期: 7
页码: 833-+
摘要: Chromatin-associated fumarase (FH) affects histone methylation via its metabolic activity. However, whether this effect is involved in gene transcription remains to be clarified. In this study, we show that under glucose deprivation conditions, AMPK phosphorylates FH at Ser75, which in turn forms a complex with ATF2 and participates in promoter activation. FH-catalysed fumarate in promoter regions inhibits KDM2A demethylase activity, and thus maintains the H3K36me2 profile and facilitates gene expression for cell growth arrest. On the other hand, FH is found to be O-GlcNAcylated at the AMPK phosphorylation site; FH-ATF2-mediated downstream events are impeded by FH O-GlcNAcylation, especially in cancer cells that display robust O-GlcNAc transferase (OGT) activity. Consistently, the FH-Ser75 phosphorylation level inversely correlates with the OGT level and poor prognosis in pancreatic cancer patients. These findings uncover a previously uncharacterized mechanism underlying transcription regulation by FH and the linkage between dysregulated OGT activity and growth advantage of cancer cells under glucose deficiency.
英文摘要: Chromatin-associated fumarase (FH) affects histone methylation via its metabolic activity. However, whether this effect is involved in gene transcription remains to be clarified. In this study, we show that under glucose deprivation conditions, AMPK phosphorylates FH at Ser75, which in turn forms a complex with ATF2 and participates in promoter activation. FH-catalysed fumarate in promoter regions inhibits KDM2A demethylase activity, and thus maintains the H3K36me2 profile and facilitates gene expression for cell growth arrest. On the other hand, FH is found to be O-GlcNAcylated at the AMPK phosphorylation site; FH-ATF2-mediated downstream events are impeded by FH O-GlcNAcylation, especially in cancer cells that display robust O-GlcNAc transferase (OGT) activity. Consistently, the FH-Ser75 phosphorylation level inversely correlates with the OGT level and poor prognosis in pancreatic cancer patients. These findings uncover a previously uncharacterized mechanism underlying transcription regulation by FH and the linkage between dysregulated OGT activity and growth advantage of cancer cells under glucose deficiency.
刊物名称: NATURE CELL BIOLOGY
英文刊物名称: NATURE CELL BIOLOGY
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学科: Cell Biology
英文学科: Cell Biology
影响因子: 20.06
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论文类别: Article
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